Induction of a long noncoding rn A Transcript, NR-045064, promotes defense gene transcription and facilitates intestinal epithelial cell responses against cryptosporidium infection

Cryptosporidium is an important opportunistic intestinal pathogen for immunocompromised individuals and a common cause of diarrhea in young children in developing countries. Gastrointestinal epithelial cells play a central role in activating and orchestrating host immune responses against Cryptosporidium infection, but underlying molecular mechanisms are not fully understood. We report in this paper that C. parvum infection causes significant alterations in long noncoding rn A (lncrn A) expression profiles in murine intestinal epithelial cells. Transcription of a panel of lncrn A genes, including NR045064, in infected cells is controlled by the NF-kB signaling. Functionally, inhibition of NR045064 induction increases parasite burden in intestinal epithelial cells. Induction of NR045064 enhances the transcription of selected defense genes in host cells following C. parvum infection. Epigenetic histone modifications are involved in NR045064-mediated transcription of associated defense genes in infected host cells. Moreover, the p300/MLL-associated chromatin remodeling is involved in NR045064-mediated transcription of associated defense genes in intestinal epithelial cells following C. parvum infection. Expression of NR045064 and associated genes is also identified in intestinal epithelium in C57BL/6J mice following phosphorothioate oligodeoxynucleotide or LPS stimulation. Our data demonstrate that lncrn As, such as NR045064, play a role in regulating epithelial defense against microbial infection. The Journ Al of Immunology, 2018, 201: 3630-3640.